Recent years have witnessed an explosion in new therapies for type 2 diabetes. For a long time, the key tools for management of the disease were diet/exercise, metformin, sulphonylureas and thiazolidenediones. The preference for orally active small molecules continued with introduction of inhibitors of enzymes DPPIV and SGLT2. However, a new era of peptide therapeutics was heralded by the discovery of the stable GLP-1 mimetic, exendin-4 in the saliva of Gila monster lizard plus its exploitation for diabetes as twice daily injectable. Further structural refinements of human GLP-1 to convey enzyme resistance by N-terminal modification and extended half-life by acylation seeded new generations of GLP-1 mimetics with greater effectiveness that extended to substantial weight loss. Concurrent realisation by diabetologists that Roux-en Y gastric bypass could induce diabetes remission by orchestrating substantial changes in circulating gut hormones spawned enthusiasm for combination therapy or development of unimolecular multi-agonists harnessing the diverse actions of GLP-1, GIP and glucagon. This lecture will chart this journey from perspective of innovative research conducted at Ulster over the past 25 years. It will assess where we are now in terms of our own research and what the future holds for new generations of peptides therapies for obesity-diabetes.